Platinum Rechallenge in Patients with Advanced Biliary Tract Carcinoma (ABTC) after Failure of Gemcitabine (Gem)-Platinum Combination: A National AGEO Retrospective Study.

4076 Background: There is no validated option beyond GEM-platinum standard 1st-line (L1) chemotherapy (CT) for ABTC. In ovarian and colon cancers, platinum rechallenge demonstrated benefit in patients who responded to a prior platinum-based CT and with a significant platinum-free interval. We aimed to assess the usefulness of platinum-based CT as 2nd (L2) or 3rd-line (L3) treatment in ABTC. Methods: Patients with ABTC who received platinum-based CT as L2 or L3 were identified from a national retrospective AGEO cohort of ATBC patients receiving L2 CT after failure of GEM-platinum L1 CT at 18 French institutions. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Results: Among 686 patients who received GEM-platinum L1 CT, 231 were given L2 CT; among them, 92 (39.8%) received a platinum-based CT as L2 (n = 70) or L3 (n = 25). Median age was 65 years (range: 25-81); 50 (54.3%) patients were men and 42 were women. The primary tumor was intrahepatic, extrahepatic and gallbladder carcinoma in 44/28/19 patients. L1 CT was GEMOX in 83 (90.2%) patients and GEMCIS in 9. At the time of platinum rechallenge, 82 (92.1%) patients had metastatic disease; ECOG PS was 0-1 in 73.6%; CA19.9 was > 400 IU/ml in 36.2%. Rechallenge regimens were 5FU-cisplatin (n = 53), FOLFOX/XELOX (n = 28), GEMOX/GEMCIS (n = 9), and carboplatin-based CT (n = 5). Overall, median L1 PFS (mPFS) was 7.2 months and median OS (mOS) from L1 was 17.4 months; mPFS and mOS from platinum rechallenge were 4.4 months (L2: 4.8; L3: 3.4) and 7.7 months (L2: 7.7; L3: 7.7), respectively. 82 patients were evaluable according to RECIST criteria; 12 (14.6%) had partial response and 40 stable disease (48.8%) (disease control rate [DCR] 63.4%). PS (0-1 vs 2-3) and CA19.9 (≤ vs > 400 IU/ml) were significantly associated with longer PFS (HR 2.41, p = 0.0016 and HR 1.88, p = 0.0350); PS, CA19.9, and reason for L1 discontinuation (toxicity/other vs progression) were significantly associated with longer OS (HR 2.17, p = 0.0019; HR 1.69, p = 0.0491; HR 1.77, p = 0.0122, respectively). Conclusions: Platinum rechallenge is an interesting option yielding a DCR over 60% in patients with ABTC.